The efficient catalytic transformation of monosubstituted alkenes into valuable terminally functionalized alkanes, such as amines, alcohols, acids and aldehydes, is of critical importance to polymer science, drug discovery, chemical biology and the bulk chemical industry. However, these transformations require breaking a textbook rule of organic chemistry: Markovnikov's rule. This rule predicts that nucleophiles will attack the more substituted carbon of an alkene. Thus, to functionalize the terminal position of unbiased alkenes with an oxygen or nitrogen nucleophile, the innate (substrate-controlled) Markovnikov selectivity must be superseded using a highly anti-Markovnikov selective catalyst-controlled process. To date, only a handful of reactions have achieved catalytic intermolecular anti-Markovnikov installation of oxygen or nitrogen. These examples have nearly all required biased substrates (such as styrenes or conjugate acceptors) to efficiently obtain anti-Markovnikov selectivity. Despite the recognition of such important transformations as top challenges in catalysis two decades ago, no synthetically useful direct, catalytic anti-Markovnikov addition of oxygen or nitrogen to unbiased alkenes has been realized to date.
The traditional approach to anti-Markovnikov functionalization of terminal alkenes has relied upon the ubiquitous hydroboration reaction (11). The wide adoption of hydroboration in organic synthesis is due to the synthetic versatility of the alkylborane products, which can be transformed into many important functionalities. Unfortunately, this stoichiometric process generates significant waste and has limited functional-group compatibility.